Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans

J Diabetes Complications. 2016 Sep-Oct;30(7):1275-81. doi: 10.1016/j.jdiacomp.2016.06.030. Epub 2016 Jul 4.

Abstract

Background: The comparative effects of acute moderate hyperglycemia and hypoglycemia on in vivo endothelial function together with pro-inflammatory and pro-atherothrombotic responses in healthy individuals have not been determined.

Methods: To investigate this question, 45 healthy subjects were compared during glucose clamp studies consisting of euinsulinemic hyperglycemia and hyperinsulinemic hyperglycemia (plasma glucose 11.1mmol/L, both with pancreatic clamps) and hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia (plasma glucose 5.1 and 2.9mmol/L, respectively). Two-dimensional Doppler ultrasound was used to determine brachial artery endothelial function.

Results: Insulin levels during euinsulinemia hyperglycemia were 194±23 and (850±49-988±114) pmol/L during all hyperinsulinemic protocols. Responses of VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 were increased (p<0.05-0.0001) during euinsulinemic hyperglycemia or hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 was increased (p<0.04) during hypoglycemia as compared to euinsulinemic hyperglycemia, and TNF-α responses were also increased during hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia (p<0.05). In vivo endothelial function was similarly blunted by acute moderate hyperglycemia or hypoglycemia.

Conclusion: In summary, acute moderate hypoglycemia and euinsulinemic hyperglycemia can result in similar endothelial dysfunction and pro-atherothrombotic responses. Fibrinolytic balance was reduced by a greater extent by hypoglycemia as compared to moderate hyperglycemia. Acutely, hyperinsulinemia can prevent the acute pro-atherothrombotic and pro-inflammatory effects of moderate hyperglycemia but not hypoglycemia.

Keywords: Endothelial function; Hyperglycemia; Hyperinsulinemia; Hypoglycemia; Inflammation.

MeSH terms

  • Adult
  • Atherosclerosis / blood*
  • Biomarkers / blood
  • Blood Glucose
  • Diabetes Mellitus
  • Endothelium / physiopathology*
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hyperglycemia / physiopathology*
  • Hyperinsulinism / physiopathology
  • Hypoglycemia / physiopathology*
  • Insulin
  • Male
  • Thrombosis / blood*

Substances

  • Biomarkers
  • Blood Glucose
  • Insulin